Combined clinical and laboratory studies of drug-induced systemic lupus erythrematosus resulting from hydralazine and procainamide administration will be carried out. A hypothesis to be studied is that N-oxidation is responsible for the formation of reactive intermediates which undergo covalent binding to nuclear material. The metabolism of these drugs will be studied in slow and fast acetylators. An attempt will be made to develop an animal model (rabbit). A second pathway of metabolism leading to potential toxicity is through epoxide formation. This will be studied for phenytoin, pronethalol and carbamazepine. Epoxide toxicity is likely to be expressed for dihydrodiolepoxides which result from epoxidation of dihydrodiol metabolites. Catechol toxicity is believed to be expressed through oxidation to an o-quinone, followed by non-enzymatic reactions with cellular components. Routes of potential toxicity through reaction with cellular constituents will be studied; the constituents most directly involved are glutathione, cysteine, proteins and nucleic acids. Studies of the cytotoxicity and mutagenicity of potentially toxic metabolites will be carried out.